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A study published in this week’s Federation of European Biochemical Societies 
(FEBS) Journal offers – for the first time – a model for the complex process 
of aggregation of a protein known as alpha-synuclein, which in turn leads to 
harmful ring-like or pore-like structures in human membranes, the kind of 
damage found in Parkinson’s and Alzheimer’s patients. 
 
The researchers at SDSC and UC San Diego also found that the destructive 
properties of alpha-synuclein can be blocked by beta-synuclein – a finding 
that could lead to treatments for many debilitating diseases. 
 
The current journal’s cover features an image from the research that helps 
illustrate the scientists’ work. 
 
“This is one of the first studies to use supercomputers to model how 
alpha-synuclein complexes damage the cells, and how that could be blocked,” 
said Eliezer Masliah, professor of neurosciences and pathology at UC San 
Diego. “We believe that these ring- or pore-like structures might be 
deleterious to the cells, and we have a unique opportunity to better 
understand how alpha-synuclein is involved in the pathogenesis of Parkinson’s 
disease, and how to reverse this process.” 
 

   
 Igor Tsigelny, project scientist in chemistry and biochemistry at UC San 
Diego and a researcher at SDSC, said that the team’s research helped confirm 
what researchers had suspected. “The present study – using molecular modeling 
and molecular dynamics simulations in combination with biochemical and 
ultrastructural analysis – shows that alpha-synuclein can lead to the 
formation of pore-like structures on membranes.” 
 
 In contrast, he said, “beta-synuclein appears to block the propagation of 
alpha-synucleins into harmful structures.” 
 
The complex calculations for the study were performed on Blue Gene 
supercomputers at SDSC and the Argonne National Labs. 
 
Tsigelny worked in collaboration with Pazit Bar-On, Department of 
Neurosciences; Yuriy Sharikov of SDSC; Leslie Crews of the Department of 
Pathology; Makoto Hashimoto of Neurosciences; Mark A. Miller of SDSC; Steve 
H. Keller in Medicine; Oleksandr Platoshyn and Jason X.J. Yuan, both in 
Medicine; and Masliah, all at UC San Diego. 
 

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